Investigating the Aggregation of α-synuclein Variants and Their Interactions with a Molecular Tweezer

The protein α-synuclein (α-syn) self-assembles under abnormal conditions into toxic aggregates thought to be a central cause of pathology in neurodegenerative diseases such as Parkinson’s Disease (PD). A promising approach for treating PD is to inhibit the abnormal self-assembly of α-syn in the brain by using small molecules called “molecular tweezers” that the Bitan laboratory has been developing. Molecular tweezers bind to lysine (Lys) residues and prevent both hydrophobic and electrostatic interactions that are key to abnormal self-assembly. The molecular tweezer CLR01 inhibits the self-assembly of α-syn in vitro and in vivo by preferentially binding to Lys at positions 10 and/or 12 and at the region spanning residues 43-58. This leads me to investigate how effective CLR01 is in preventing aggregation when the amino acid at the binding site is substituted, by using Lys to Ala variants of α-syn at positions 43 and 58. I hypothesize that CLR01 will prevent more effectively aggregation in the wild type (WT) than it will in the two variants because essential binding sites will be missing in these variants. As my main experimental method, I use the Thioflavin-T fluorescence assay to measure the amount and kinetics of -pleated sheet formation, which is analogous to α-syn aggregation regardless of the absence or concentration of CLR01. This study will provide insight into the preferred binding site of CLR01 and the behavior of α-syn containing amino acid substitutions and thus will increase our understanding of this important mechanism underlying PD and potentially direct future drug development efforts

Mathematical Aspects of the Periodic Law

We review different studies of the Periodic Law and the set of chemical elements from a mathematical point of view. This discussion covers the first attempts made in the 19th century up to the present day. Mathematics employed to study the periodic system includes number theory, information theory, order theory, set theory and topology. Each theory used shows that it is possible to provide the Periodic Law with a mathematical structure. We also show that it is possible to study the chemical elements taking advantage of their phenomenological properties, and that it is not always necessary to reduce the concept of chemical elements to the quantum atomic concept to be able to find interpretations for the Periodic Law. Finally, a connection is noted between the lengths of the periods of the Periodic Law and the philosophical Pythagorean doctrine.Comment: 20 pages, PDF fil

Erratum: "A Gravitational-wave Measurement of the Hubble Constant Following the Second Observing Run of Advanced LIGO and Virgo" (2021, ApJ, 909, 218)

[no abstract available

GW190814: gravitational waves from the coalescence of a 23 solar mass black hole with a 2.6 solar mass compact object

We report the observation of a compact binary coalescence involving a 22.2–24.3 Me black hole and a compact object with a mass of 2.50–2.67 Me (all measurements quoted at the 90% credible level). The gravitational-wave signal, GW190814, was observed during LIGO’s and Virgo’s third observing run on 2019 August 14 at 21:10:39 UTC and has a signal-to-noise ratio of 25 in the three-detector network. The source was localized to 18.5 deg2 at a distance of - + 241 45 41 Mpc; no electromagnetic counterpart has been confirmed to date. The source has the most unequal mass ratio yet measured with gravitational waves, - + 0.112 0.009 0.008, and its secondary component is either the lightest black hole or the heaviest neutron star ever discovered in a double compact-object system. The dimensionless spin of the primary black hole is tightly constrained to �0.07. Tests of general relativity reveal no measurable deviations from the theory, and its prediction of higher-multipole emission is confirmed at high confidence. We estimate a merger rate density of 1–23 Gpc−3 yr−1 for the new class of binary coalescence sources that GW190814 represents. Astrophysical models predict that binaries with mass ratios similar to this event can form through several channels, but are unlikely to have formed in globular clusters. However, the combination of mass ratio, component masses, and the inferred merger rate for this event challenges all current models of the formation and mass distribution of compact-object binaries

Eliminate Final Exams in Intro to Flight Through the Use of Portfolios?

A portfolio can be an extremely powerful tool to determine the degree of learning experienced by a student throughout the semester, and to force the student into a higher level of reflective learning and meta-cognition not generally possible for the student by studying for and taking the traditional in-class, timed final exam. Portfolios have been common in art, photography, journalism, business, architecture and other professions for quite some time. Strong justification can be found in learning theory for using Portfolios in engineering. Some of the numerous different types of portfolios will be briefly introduced in this paper. Portfolios have not, however, found widespread use within engineering. Even though engineering design provides the most immediately obvious application of portfolios within engineering, different kinds of portfolios can be implemented across the engineering curriculum. This paper will review the existing body of literature and specifically address the results of using portfolios in an Introduction to Flight course given to Sophomore year students in the Fall of 2004 at the University of Dayton. Feedback was solicited from the students throughout the semester to ensure open and clear communication and understanding. It was found to be important to address student fears immediately and answer their questions about the entire process and the instructor\u27s expectations. This communication eased the initial discomfort with the concept of using portfolios. By the time the students had submitted their portfolios, all of the students were extremely positive about the entire portfolio experience. Most importantly, the portfolios submitted made clear to both the student and instructor, the level of understanding and comprehension of the breadth and depth of the subject being examined in a manner not possible through the use of a traditional in-class timed final exam